Ductal lavage microcatheter with user activated valve and Nitinol introducer

ABSTRACT

A medical instrument including a ductal access device comprising a low profile, ergonomic manifold hub usable to introduce fluids into a breast duct and collect ductal fluid samples including ductal epithelial cells and clumps of ductal epithelial cells from within a breast duct. The ductal access device also comprises an elongated access catheter having a distal end, one lumen and dimensions which permit introduction of the distal end through a ductal orifice so that a distal end of the catheter may be positioned distal to the ductal sphincter of a human breast. The medical instrument may also include and activate valve and a Nitinol introducer.

FIELD OF THE INVENTION

The present invention relates to a medical instrument having at least aportion that is introduced into the body of a mammal in order to performdiagnostic or therapeutic medical procedures, more specifically, thepresent invention relates to a medical instrument useable during adiagnostic or therapeutic medical procedure that is sized forintroducing into a breast duct through a ductal orifice.

BACKGROUND OF THE INVENTION

The breast is a specialized, glandular structure including a system ofcomplicated breast ducts that radiate from the nipple and that are boundtogether by fairly dense connective tissue. Each of these breast ductsincludes an associated ductal orifice on the surface of a nipple throughwhich ductal fluid may be expressed. Each duct includes a series ofsuccessive interlobular branches that drain through the main,lactiferous branch, which terminates and exits the breast at the nipplevia the associated ductal orifice. Immediately proximate the ductalorifice, each lactiferous duct includes a lactiferous sinus in whichductal fluid may accumulate. A ductal sphincter resides within thelactiferous sinus and prevents ductal fluid from unintentionally exitingthe breast duct through its associated ductal orifice.

Breast cancer is believed to begin in the lining of these breast ducts.For several decades significant members of the medical communitydedicated to studying breast cancer have believed and shown that thecytological analysis of cells retrieved from nipple discharge fluid fromwithin breast ducts may provide valuable information leading toidentifying patients at risk for breast cancer. Indeed, Papanicolaoucontributed to the genesis of such a possibility of a “Pap” smear forbreast cancer by analyzing the cells contained in nipple discharge. Morerecently, cancer specific markers have been detected in ductal fluidobtained by nipple aspiration. However, the retrieval techniques andinstruments used by these members of the medical community did notroutinely obtain meaningful ductal fluid samples.

In their attempts to retrieve the breast duct fluid sample includingductal epithelial cells, practitioners introduced wash fluids into abreast duct using indwelling hair-like single lumen catheters. After thefluid was introduced into the duct, the fluid introduction catheterswere removed. Then, externally applied nipple aspiration techniques orexternal pressure applied to the breast were used to collect samples ofthe ductal fluid. However, these techniques required that significant,sometimes painful, pressure be created on the nipple surface or alongthe sides of the breast to overcome the fluid retaining properties ofthe ductal sphincter. Also, these techniques did not routinely providemeaningful ductal fluid samples with a sufficient number of ductalepithelial cells for a meaningful cellular analysis. These techniquestypically caused the recovery of samples with twenty or fewer ductalepithelial cells. Additionally, these techniques did not provide sampleswith cell clusters of 10 or more cells. As a result, the obtained fluidsamples could not consistently provide an accurate indication of whetheror not the duct from which they were retrieved included precancerous orcancerous cells. Consistent, meaningful ductal epithelial cell sampleshave been provided by the medical instrument disclosed in U.S. Pat. No.6,413,228 to Hung et al. that is hereby incorporated by reference in itsentirety.

Other medical instruments, such as those used during galactography, areintroduced into the breast duct in order to visually determine thepresence of cancerous cells within a breast duct. However, these devicestypically extend a significant distance out of the breast duct duringthe performed procedure. These distances may be twelve inches orgreater. As a result, when an operator is not holding the tool, themoment created by the weight and length of the section of the instrumentextending out of the duct may cause the indwelling portion of theinstrument to engage the sidewalls of the duct, torque and/or kink theduct and distort the nipple. These effects on the duct and nipple mayimpede the procedure by twisting or crimping the indwelling portion ofthe instrument, possibly injuring the patient's duct and causingsignificant discomfort to the patient. As a result, a patient musteither endure the pain and discomfort caused by these long instrumentsor an attendant must constantly support the instrument above the patientduring the medical procedure.

However, in the confined space around an operating table and in the areasurrounding a nipple surface, it is not practical to have an attendantconstantly holding the end of the instrument that is extending into thebreast duct. Therefore, prior to receiving the procedure, a patient mustdecide to either experience discomfort during the procedure or choosenot to have the procedure performed. Prior art instruments are also notergonomically designed for easy grasping and adjusting by a practitioneror attendant while acting in the area surrounding a nipple.

SUMMARY OF THE INVENTION

In accordance with one aspect of the present invention, a device forbeing introduced and positioned within a breast duct for introducing orremoving material within the breast duct is provided. The apparatuscomprises a manifold hub comprising a sealing fitting for sealing abouta ductal introducer extending through the manifold hub at one end of themanifold hub the sealing fitting including an aperture that may berepeatedly opened and closed, the sides of the manifold hub comprisingtwo opposing flexible arms connected at one end to the base of the huband unconnected at the other end and substantially parallel to oneanother, the arms are held in a sprung position such that theunconnected ends of said arms compress the sealing fitting such that theaperture is closed and when the arms are compressed, the unconnectedends of the arms no longer compress the sealing fitting and the apertureis opened. The sealing fitting may be comprised of a silicone gasket.The apparatus may also include springs that are located between saidflexible arms and the body of said hub such that the springs keep saidarms in actuated position. The free ends of the arms may be interlockinghooks. The ductal introducer may be a ring shaped handle. The ductalintroducer may be made of a flexible material such as Nitinol and mayhave a distal tip that tapers from approximately 0.025 inches toapproximately 0.008 inches.

In yet another aspect of the present invention, a method for obtainingcellular material from a human breast milk duct is provided. The methodmay include using a device comprising a manifold hub comprising afitting for sealing about a ductal introducer extending through saidmanifold hub at one end of said manifold hub said fitting including anaperture that may be repeatedly opened and closed, the sides of saidmanifold hub comprising two opposing flexible arms connected at one endto the base of said hub and unconnected at the other end andsubstantially parallel to one another, said arms are held in a sprungposition such that said unconnected ends of said arms compress saidfitting such that said aperture is closed and when said arms arecompressed, said unconnected ends of said arms no longer compress saidfitting and said aperture is opened; and including the steps ofinserting the introducer into the internal passageway of a breast duct;and advancing the catheter into the breast duct.

In still yet another aspect of the present invention, a method forobtaining cellular material from a human breast milk duct is provided.The method may include using a device comprising a manifold hubcomprising a fitting for sealing about a ductal introducer extendingthrough said manifold hub at one end of said manifold hub said fittingincluding an aperture that may be repeatedly opened and closed, thesides of said manifold hub comprising two opposing flexible armsconnected at one end to the base of said hub and unconnected at theother end and substantially parallel to one another, said arms are heldin a sprung position such that said unconnected ends of said armscompress said fitting such that said aperture is closed and when saidarms are compressed, said unconnected ends of said arms no longercompress said fitting and said aperture is opened; and including thesteps of inserting the introducer into the internal passageway of abreast duct advancing a sheath into the breast duct; and advancing thecatheter into the breast duct.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a perspective view of a medical instrument according toaspects of the present invention;

FIGS. 2A and 2B are cross sections of alternative embodiments of themedical instrument illustrated in FIG. 1;

FIG. 3 is an exploded perspective view of the medical instrument of FIG.1;

FIG. 4 is a top view of the medical instrument of FIG. 1 with infusionand collection lines extending between a manifold hub and respectiveinfusion and collection devices;

FIG. 5 is a side view of the medical instrument illustrated in FIG. 1carrying infusion and collection lines;

FIG. 6 is another perspective view of the medical instrument illustratedin FIG. 1;

FIGS. 7 and 8 illustrate an alternative embodiment of the medicalinstrument according to aspects of the present invention;

FIGS. 9-11 illustrate a method for introducing the medical instrument ofFIG. 1 into a breast duct using a stiff introducer; and

FIGS. 12-13 illustrate an alternative method for introducing the medicalinstrument of FIG. 1 into a breast duct using a flexible introducer.

FIGS. 14-17 illustrate an alternative embodiment of the medicalinstrument according to aspects of the present invention including aductal lavage microcatheter with user activated valve and Nitinolintroducer with a ring shaped handle.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates an embodiment of a low profile, single lumen medicalinstrument 10 for performing a medical procedure within a breast duct.As used herein, the phrase “medical procedure” may include preparatoryprocedures, diagnostic procedures or therapeutic procedures. Theseprocedures could include the steps of delivering material(s) into thebreast duct and/or retrieving material(s) from within the breast duct.

In an embodiment, the medical instrument 10 may be used to infuse ductalwash fluid delivered to the manifold hub 20 into the breast duct, andcollect or draw up ductal fluid samples, including hundreds of ductalepithelial cells and/or cell clusters of greater than ten cells, fromwithin the breast duct for analysis. In another embodiment, the medicalinstrument 10 may be used to infuse a diagnostic agent or therapeuticagent into a breast duct. As shown in FIGS. 1-8, the instrument 10 mayalso include a member 11 for securing the instrument 10 to a patient.The securing member 11 may have a biocompatible adhesive on one side forcontacting and attaching the instrument 10 to the patient. The member 11is sized to prevent movement of the manifold hub 20 relative to the bodyof the patient. In an embodiment illustrated in FIGS. 7 and 8, sections11A and 11B of the member 11 may be folded onto each other so that thesize of the securing member 11 may be adjusted to the patient and theforces created during the procedure. Additionally, the member 11 may bepositioned distal a spacer 90 (discussed below).

As illustrated in FIGS. 1-6, the medical instrument 10 includes amanifold hub 20 and a ductal access catheter 40 that extends from adistal end 21 of the manifold hub 20. The access catheter 40 is sized toaccesses the breast duct. As illustrated, the manifold hub 20 may have alow profile (height) in a direction that extends parallel to the lengthof the catheter 40. As illustrated in FIGS. 1-6, the height of themanifold hub 20 may be less than its length (the direction it extendsperpendicular to the length of the catheter 40). In a first embodiment,the manifold hub 20 may have a width in a range from about 0.25 inch toabout 0.375 inch and a height in a range from about 0.75 inch to about1.0 inch. In another embodiment, the manifold hub 20 has an internalfluid capacity of 1 ml or less. The low profile of the manifold hub 20will help to prevent a pivot point from being formed at a location alongthe length of the catheter 40 at which a large torque may be applied tothe duct of a patient during a medical procedure. By eliminating or, atleast, significantly reducing any torquing of the duct, the duct willnot be kinked, closed due to a change in the position of ductal tissueor injured due to the catheter 40 pushing against the epithelial liningof the duct. The instrument 10 also has an ergonomic design that allowseasily handling and grasping by an attendant or practitioner so that themanifold hub 20 and catheter 40 may be easily manipulated.

In the event that the manifold hub 20 needs to be spaced from the nipplesurface, a retractable spacer 90 may be positioned on the distal end ofthe manifold hub and at the proximal end of the catheter 40 as shown inFIGS. 7 and 8. The retractable spacer 90 may have a spacing distance inthe range from about 1 mm to about 10 mm, most typically in the range ofabout 5 mm. In a first embodiment, the retractable spacer 90 may includea first spacing member 92 received within a second spacing member 93.Alternatively, the first spacing member 92 may telescopically receivethe second spacing member 93. In this embodiment, the first member 92 issecured against movement relative to the manifold hub 20, while thesecond member 93 is moveable relative to both the first member 92 andthe manifold hub 20. In an alternative embodiment, both of the spacingmembers 92, 93 are moveable relative to the manifold hub 20. Thedistances required for spacing the manifold hub 20 from the surface ofthe nipple, for example distances of between about 15 mm and 20 mm, maybe controlled by locking the spacing members 92, 93 in an extendedposition (FIG. 8). Alternatively, the retractable spacer 90 may belocked in a retracted position (FIG. 7). In an alternative embodiment,the retractable spacer 90 includes a single moveable spacing member 95that slidably receives a portion of the manifold hub 20 to achieve theretracted position and that may be locked at the end of the manifold hub20 to achieve the extended position. In any of the above-discussedembodiments, the spacing members 92, 93, 95 may be rotated relative toeach other and the manifold hub 20 in order to lock each spacing member92, 93 and 95 against translational movement relative to each other andthe manifold hub 20. Any known rotational locking system for telescopingmembers may be used. Alternatively, the spacing members 92, 93, 95 maybe snapped into a locked position using well known snap locks. Whenadditional spacing is needed, members 92, 93, 95 of different sizes ormore than two telescoping members may be provided.

The manifold hub 20 may be formed of a transparent material so that anattendant or practitioner may easily view fluid(s) and material(s)within the manifold hub 20. The transparent material may be a plastic,such as ABS plastics or other known plastic materials. As illustrated inFIGS. 1-8, an embodiment of the manifold hub 20 may have a substantially“F” shape.

As shown in FIGS. 2A, 2B and 4, the manifold hub 20 includes a firstport 30 for connecting to an infusion tube 34 through which materialsincluding wash fluids, diagnostic agents or treatment agents aredelivered from an infusion device 38 to the first port 30, the manifoldhub 20 and, eventually, the ductal access catheter 40. The connectedinfusion device 38 may include a syringe or other known fluidcontainers. In an embodiment, the infusion device 38 may include a fluidreceptacle, such as a bag or a container, positioned at a location abovethe breast of the patient. In this embodiment, the height of thecontainer above the breast of the patient and gravity are used todeliver the fluid from the infusion device 38 to the infusion tube 34.

As shown in FIGS. 2A, 2B and 4, the manifold hub 20 also includes asecond port 32 for connection to a collection tube 36. Ductal fluidsamples collected from within the breast duct may be delivered from themanifold hub 20 to a collection receptacle 39 via the collection tube36. The collection receptacle 39 may include a syringe or other knownfluid collection device including a medical fluid bag or container. Inan embodiment, the collection receptacle 39 may include or be connectedto a source of negative pressure so that an area of low pressure may becreated within the collection tube 36 and, if needed, the manifold hub20 for assisting in the delivery of the retrieved ductal fluid sample tothe collection receptacle 39. The area of low pressure, for example avacuum in an embodiment, may be created using a bulb syringe, ahand-operated vacuum source, a foot operated vacuum source or motorcontrolled vacuum source. These vacuum sources may include a pump thatcreates negative pressure within the collection tube 36. In addition toa source of lower pressure, or in place of the source of lower pressure,low pressure within collection tube 36 may be created by infusing fluidinto the manifold hub 20, thereby increasing the pressure within themanifold hub 20 relative to the collection tube 36. In any of theseembodiments, the collection receptacle 39 may be positioned at alocation below the patient during the procedure so that the collectedductal fluid sample may be delivered to the receptacle 39 by gravity.

The first and second ports 30, 32 may include an opening along thesidewall of the manifold hub 20 that is round, oval or any othergeometric shape conducive to fluid flow either into the duct or out fromthe duct as shown in FIGS. 2A and 2B. The diameter of the ports 30, 32may be that diameter which is suitable to achieve a desired flow rateinto the duct or aspiration or collection rate out from the duct. Thus,the diameters of the ports 30, 32 may be in a range from about 0.060inches to about 0.090 inches. One side port 30, 32 may be larger orsmaller than the other, especially where such differential port sizeprovides a desired flow rate into or out from one of the lumens, or anoverall lavage efficiency of infusion and aspiration or collection oflavage and ductal fluid.

FIGS. 1-6 illustrate that the first and second ports 30, 32 and theirassociated tubes 34, 36, respectively, are positioned within a connectorhousing 25 that extends transverse to the longitudinal axis of themanifold hub 20 and the catheter 40. The connector housing 25 may beintegrally formed with the manifold hub 20 as a unitary element.Alternatively, the connector housing 25 may be formed separate of themanifold hub 20 and secured to the manifold hub 20 as discussed belowwith respect to the catheter 40. The connector housing 25 includes twochannels 26 that each receives one of the tubes 34, 36. The channels 26extend from the ports 30, 32 on the manifold hub 20 to the outer, endsurface of the connector housing 25. Each channel 26 aligns the receivedtube 34, 36 with its respective manifold hub port 30, 32 for easy,reliable and quick connection of the tubes 34, 36 to their respectiveports 30, 32. The channels 26 also support the tubes 34, 36 at theirpoint of connection to their ports 30, 32 so that the tubes 34, 36 donot create a moment (that may torque the duct) about the point wherethey connect to their respective ports 30, 32. The connector housing 25may also include contoured sidewalls 28 with integrally formed, orotherwise secured, ridges 29 that may be gripped by an attendant or apractitioner. The contoured sidewalls 28 permit easy grasping by theattendant or practitioner and allow the attendant or practitioner toorient the instrument 10 during a procedure without looking at theinstrument 10.

In an embodiment shown in FIG. 2B, the first and second ports 30, 32 mayinclude posts 35 that extend within connector housing 25 and receive theflexible infusion and collection tubes 34, 36. In an embodiment, theinfusion and collection tubes 34, 36 may be formed of flexible tubingsuch as surgical tubing. However, the tubes 34, 36 may be formed of anyflexible material including a flexible plastic. In one embodiment, thetubes 34, 36 are formed of flexible PVC.

The posts 35 may securely receive the tubes 34, 36 when the tubes 34, 36are positioned over, or within, the posts 35. Alternatively, the ports30, 32 and their associated posts 35 may include luer lock fittings (notshown) that cooperate with corresponding luer lock fittings on a firstend of the tubes 34, 36. The second end of the tubes 34, 36 may alsoinclude luer lock fittings that mate with standard luer lock fittings onthe syringes or other fluid containers. The luer lock fittings may beeither male or female fittings. As discussed herein, the syringes andother fluid containers may carry and infuse saline, diagnosticmaterials, such as contrast materials, and therapeutic treatmentmaterials into the infusion tube 34. The tubes 34, 36 may be secured tothe posts 35 of the manifold hub 20 and the luer locks using a UVcurable adhesive or other known bonding agents. In alternativeembodiments, the tubes 34, 36 may be secured to the manifold hub 20 andthe luer locks by overmolding.

As shown in FIGS. 1-6, the first port 30 may be positioned adjacent thesecond port 32 along the perimeter of the manifold hub 20. In theillustrated embodiment, the circumferentially adjacent ports 30, 32 arespaced the same longitudinal distance from the first and second ends 22,24 of the manifold hub 20. This spacing of the ports 30, 32 provides fora compact and low profile manifold hub 20 that, as discussed above, willnot create a moment and associated forces that toque the duct when themanifold hub 20 is positioned on the patient and free of support from apractitioner or other attendant.

The second port 32 may be circumferentially spaced any distance from thefirst port 30 around the wall of the manifold hub 20. In an embodiment,the first port 30 may be between forty-five and ninety degrees offsetfrom the second port 32 around the circumference of the manifold hub 20.In an alternative embodiment, the first port 30 may be circumferentiallyoffset along the manifold wall from the second port 32 by between ninetyand one hundred-eighty degrees. In an embodiment, the first port 30 iscircumferentially offset from the second port 32 by about onehundred-eighty degrees so that the first and second ports 30, 32 opposeeach other within the manifold hub 20.

In an alternative embodiment, it is possible for the second port 32 tobe located along the hub 20 at a position that is spaced a greaterlongitudinal distance away from the catheter 40 than the first port 30.In this embodiment, the second port 32 may be used to collect the fluidthat enters the manifold hub 20 from the collection catheter 40. Forexample one port may be located about 2.0 cm from the distal tip of thecatheter 40 and one port may be located about 2.5 cm from the distal tipof the catheter 40.

The tubes 34 and 36 may each include a one-way check valve 39 (FIG. 2A)to control the fluid flow into and out of the manifold hub 20. The checkvalve 39 in the tube 34 may prevent, for example, wash fluid fromflowing back into a syringe connected to tube 34 after being infusedinto tube 34. Similarly, check valve 39 in tube 36 may be used toprevent retrieved ductal fluid samples in tube 36 from flowing back intothe manifold hub 20. In an alternative embodiment, pinch clamps on thetubes 34, 36, may replace one or both of the check valves 39. Forexample, a check valve 39 may be positioned within the infusion tube 34and a conventional pinch clamp may be positioned on the collection tube36. Other known devices for controlling the direction and timing offluid flow within a tube 34, 36 may also be used.

As shown in FIGS. 1-6, the catheter 40 includes a thin walledmicrocatheter 41 that is secured to the manifold hub 20. In a firstembodiment, the microcatheter 41 is integrally formed as part of themanifold hub 20. In another embodiment, the microcatheter 41 is formedas a separate piece and then secured to the manifold hub 20 bymicrowelding or a UV curable adhesive. Other known techniques forsecuring the microcatheter 41 to the manifold hub 20 could be used. Inany of the above-discussed embodiments, the catheter 40 may be coatedwith a known agent to provide a lubricious coating that allows it to beeasily introduced into the breast duct openings. The coating may includea lubricant, a cleaning agent, anesthetic and/or a dilating agent. Themicrocatheter 41 may be formed of any known biocompatible material suchas FEP. The catheter 40 may have an outer diameter in a range from about0.01 inch (about 0.25 mm) to about 0.05 inch (about 1.25 mm) with aninner lumen 43 having a diameter in the range from about 0.008 inch(about 0.2 mm) to about 0.047 inch (about 1.2 mm). In an embodiment, themicrocatheter 41 has an inner lumen 43 having an outer diameter of about0.030 inch (about 0.762 mm) and an inner diameter of about 0.025 inch(about 0.63 mm).

The catheter 40 may include length indicia (not shown) on an outersurface of the catheter 40 that permits a user to determine the depth towhich the distal end of the catheter has been introduced into the breastduct. In an alternative embodiment, the catheter 40 could include anintegrally formed or attached stop element (not shown) that preventsinsertion of the catheter into the duct beyond a predetermined distance.In one embodiment, the stop element may comprise a knob on the catheter40 having an increased diameter for preventing the distal portion of thecatheter 40 from entering a duct a greater distance than the knob isspaced from the distal end of the catheter 40.

As illustrated in FIGS. 1-7, the catheter 40 may be tapered along itslength to make a smooth transition with a received introducer 50 so thata perceptible transition between the catheter 40 and the introducer 50that would cause any pain to the patient is not formed and felt by thepatient. The catheter 40 may also include an atraumatic distal tipportion 42 at its distal end. The distal tip portion 42 may be tapered,contoured and/or rounded so as to produce an atraumatic tip that willreduce or eliminate trauma to the duct upon entry through the ductalorifice and introduction into the ductal lumen past the ductalsphincter. The distal tip portion 42 may also reduce or eliminate traumaupon withdrawal of the catheter 40 from the duct after the medicalprocedure, such as ductal lavage or the infusion of a diagnostic and/ortreatment agent, has been completed. The tip portion 42 may be composedof a soft polymeric material, e.g. including polyvinyl chloride,polyethers, polyamides, polyethylenes, polyurethanes, copolymers thereofand the like. The tip portion 42 may have a diameter in the range fromabout 0.012 inches (about 0.031 mm) to about 0.020 inches (about 0.051mm). In an embodiment, the tip portion 42 has a diameter in the rangefrom about 0.014 inches (about 0.036 mm) to about 0.018 inches (about0.046 mm). The length of the tip portion 42 (extending from the distalend of the distal portion of the catheter 40 toward the proximal end ofthe catheter 40) may be in a range from about 0.10 inch (about 0.25 cm)to about 1.0 inch (about 2.5 cm), more typically in the range from about0.20 inch (about 0.50 cm) to about 0.70 inch (about 1.8 cm).

The stiffened distal portion of the catheter 40, including the distaltip 42, may have an average bending stiffness in the range from about0.010 inch-lbs to about 0.5 inch-lbs. The catheter 40 may also have astiffness that is similar to that of a heavy suture (approximately 0.025OD). The proximal portion of the catheter 40 may have a cross-sectionalgeometry and/or size that inhibits insertion through the ductal orificeand into the ductal lumen.

A Touhy-Borst fitting 70 may be positioned at a proximal end 22 of themanifold hub 20 to allow a user to easily receive and move the catheter40 over an introducer 50 as shown in FIGS. 1-6. The Touhy-Borst fitting70 is positioned at the end of the manifold hub 20 to cover and seal theopening 77 through which an introducer 50 (discussed-below) including aguidewire, stylet, dilator or the like may extend. The Touhy-Borstfitting 70 comprises a silicone plug 72 including a small aperture 74for receiving the introducer 50, and a threaded cap 76. When the cap 76is rotated in a first direction, the silicone plug 72 is altered and thesize of the aperture 74 is reduced. This results in the silicone plug 72forming a seal around the inserted introducer 50. When the cap 76 isturned in a second, opposite direction, the aperture 74 and created sealopen, thereby allowing the introducer 50 to be removed. The siliconeplug 72 may also be closed to seal the proximal end of the manifold hub20 so when the introducer 50 is not present so that the distal end ofthe manifold hub 20 is sealed against fluid flow when the proximal end22 is free of an introducer 50.

The introducer 50 may be located within the manifold hub 20 to assist inplacing the catheter 40 into the breast duct and ductal lumen via theductal opening as shown in FIG. 1. The introducer 50 may include atapered dilator, a series of progressively larger diameter dilators, aguidewire, including tapered guidewires, a stylet or other knownintroducers. As illustrated, the introducer 50 will pass through theTouhy-Borst fitting 70 at the proximal end 22 of the manifold hub 20 sothat the introducer 50 may be removed after positioning of the catheter40 and prior to the infusion/collection of the wash fluid. As discussedabove, prior to being inserted into the breast duct, the Touhy-Borstfitting 70 may be turned down over the introducer 50 during introductionand then backed off when the catheter 40 has been positioned within thebreast duct to the desired depth. The introducer 50 may be formed of astiff material such as a metal wire or a flexible plastic cord. In anembodiment, the introducer 50 may be formed of stainless steel or aflexible material such as polypropylene monofilament. In an alternativeembodiment, the introducer 50 may be formed of multiple materials or thesame materials having different stiffnesses. As a result, the introducer50 may have sections that are more flexible than adjacent sections ofthe same introducer 50. As a result, for example, the introducer 50 mayhave a first, stiff portion for guiding the introducer 50 within theductal lumen and a second, flexible portion that allows the introducer50 to conform to the shape of the ductal lumen or lumen branch intowhich it is introduced. In any of the above-discussed embodiments, theintroducer 50 may be coated with a liquid or dry lubricant material thatreduces the friction between the introducer 50 and the breast ductduring the introduction and advancement of the introducer 50 in theduct.

The introducer 50 may be made of metal or plastics, including shapememory metals and plastics, and may have a tapered and/or an atraumatictip for gently probing and accessing a breast duct. Preferably, atapered tip 52 will extend distally of the catheter 40 during theintroduction of the catheter 40 into the breast duct. After access ofthe duct is complete, the introducer 50 may be withdrawn, theTouhy-Borst fitting 70 may be closed and the indwelling catheter 40 maybe positioned at a location distal to the ductal sphincter. Theintroducer 50 may have an outer diameter of from about 0.005 inch toabout 0.030 inch. In an embodiment, the introducer 50 has an outerdiameter of about 0.010 inch. The introducer 50 may extend through themanifold hub 20 and the lumen of the catheter 40. The introducer 50 maybe tapered over its length.

During the process of introducing the catheter 40 into the duct, aductal opening is located on the surface of a nipple by a practitioneror attendant and a first introducer 50 is advanced through the ductalopening into the duct. The introducer 50 may be a long flexible guidewire, a shorter dilator or any of the other above-mentioned introducers.Prior to, or after the introducer 50 is positioned within the duct, themanifold hub 20 and catheter 40 may receive the first or a secondintroducer 50. As previously discussed, the Touhy-Borst fitting 70 maybe locked about the received introducer 50 to form a fluid tight seal atthe distal end of the manifold hub 20 so that fluid does not exit themanifold hub 20 around the introducer 50 during the insertion catheter40 into the duct (See FIGS. 9, 10, 12 and 13).

When the catheter 40 is positioned within the duct as intended, theTouhy-Borst fitting 70 is opened and the introducer 50 removed (See FIG.11). The Touhy-Borst 70 may then be closed again to seal the hub 20.Fluid is then introduced into the manifold hub 20, through the catheter40 and into the breast duct until resistance is met during the infusion.At this time, it is assumed that the duct is filled. The infusion tube,for example tube 34, may then be closed and the fluid allowed to remainin the duct for a preselected time. During this preselected time, thebreast may be massaged and squeezed to stimulate mixing of the washfluid and ductal fluid, and also ultimately to encourage the fluid toleave the duct and enter the manifold hub 20. The collection tube, forexample tube 36, may be opened and the breast squeezed to urge the fluidto progress through the catheter 40 and into the manifold hub 20. Ifdesired, when cloudy return fluid is seen in the hub 20 (which may betransparent or include a transparent window), the infusion tube 34 maybe opened and fluid infused into the manifold hub 20 to push the ductalfluid sample that has collected in the hub 20 into the collection tube36 and a waiting collection receptacle. Alternatively, and possiblyadditionally, aspiration pressure may be applied within the manifold hub20 and at the collection tube 36 to aspirate any fluid remaining in thehub 20 into the collection receptacle. The process is repeated eitherfollowing another infusion of fluid into the duct or by another round ofsqueezing to encourage return and collection of the infused fluid andcellular material from within the breast duct.

FIGS. 14-17 are schematic diagrams illustrating an alternativeconstruction of a ductal access device. In a preferred embodiment of theinvention, the device includes a manifold hub 20 and a ductal accesscatheter 40 that extends from a distal end 21 of the manifold hub 20with a centrally disposed single lumen which extends the length of thecatheter 40. Catheter 40 includes a tubular introducer pathway adaptedto slideably receive a ductal introducer 50 therein. For ease ofexplanation, as used herein the term “introducer” is defined to includeguidewires, dilators, stylettes or portion of any of these that may beinserted within a ductal orifice or a passageway of a catheter sized toaccess a breast duct.

As illustrated, the manifold hub 20 may have a low profile (height) in adirection that extends parallel to the length of the catheter 40. Inanother construction, hub 20 has a low profile so as to reduce thetorque on the breast nipple after insertion of catheter 40. Thisovercomes the excessive generated torque on the breast nipple known tocause obstruction of ductal fluid due to compression of the tissue.Thus, improved collection of ductal cellular material is provided.

The manifold hub 20 is coupled to the proximal end 45 of the ductalaccess catheter 40. In a preferred construction, hub 20 includestransparent material so that the user may visualize the flow to and fromthe breast duct during a lavage procedure. The transparent material maybe plastic, such as ABS plastics or other known plastic materials. Asillustrated in FIGS. 14-17, an embodiment of the manifold hub 20 mayhave a substantially “U” shape.

A fitting 70 may be positioned at a proximal end 22 of the manifold hub20 to allow a user to easily receive and move the catheter 40 over anintroducer 50. The fitting 70 is positioned at the end of the manifoldhub 20 to cover and seal the opening 77 through which an introducer 50including a guidewire, stylet, dilator or the like may extend. Thefitting 70 comprises a silicone gasket including a small aperture 74 forreceiving the introducer 50, and a cap 76. The cap 76 locks the silicongasket to the manifold hub 20 thus maintaining a seal between the huband the gasket. The gasket may be made of any suitable flexiblebiocompatible material. Around the neck of the silicone gasket are apair of interlocking hooks 110 which at the terminus of flexible sidearms 100 which are part of the main body of the manifold hub 20. Locatedbetween the flexible side arms and the manifold hub are one or moresprings 120 that force the flexible arms 100 away from the main body ofthe manifold hub 20. As the springs 120 force the flexible side arms 100away from the manifold hub 20, the interlocking hooks 110 at the end ofthe flexible side arms 100 apply pressure to opposite sides of thefitting 70. This results in the fitting 70, which may be comprised ofsilicone or any other flexible material, to compress around the aperture74 forming a seal around the inserted introducer 50. When pressure isapplied to the flexible arms 100 thus compressing the springs 120, theinterlocking hooks 110 are actuated apart thus releasing pressure on thesilicon gasket and thus breaking seal around the inserted introducer 50.The flexible side arms 100 and the interlocking hooks 110 may beconstructed of metal or plastic or a combination thereof.

In an alternative embodiment, the manifold hub 20 is comprised of asingle flexible arm 100 with a single hooked end 110 which, whenactivated, opens or closes the fitting 70.

The introducer 50 may be located within the manifold hub 20 to assist inplacing the catheter 40 into the breast duct and ductal lumen via theductal opening as shown in FIGS. 9-13. The introducer 50 may include atapered dilator, a series of progressively larger diameter dilators, aguidewire, including tapered guidewires, a stylet or other knownintroducers. As illustrated, the introducer 50 will pass through thefitting 70 at the proximal end 22 of the manifold hub 20. The introducerof the present invention may consist of two parts, a wire and a ringshaped handle located at the end of the introducer. The introducer 50has a diameter equal to or slightly less than the ID of the catheter 40.The length of the introducer 50 may extend approximately 20-30 mm beyondthe distal end of the catheter 40 when the introducer is fully seated.The extended length of the introducer 50 beyond the distal end of thecatheter 40 allows the introducer to be used as a dilator prior to theinsertion of the catheter in the breast duct. As illustrated in FIG. 18,the distal end of the introducer 50 may be tapered. The distal tip ofthe introducer 50 may be tapered to an OD in the range of 0.008 to 0.010inches from the proximal end of the introducer that may have an OD equalto or slightly less than the ID of the distal end of the catheter 42.The small diameter allows for easier insertion of the introducer intothe breast milk duct. The introducer 50 may be formed of a stiffmaterial such as a metal wire or a flexible material such as plastic. Inan embodiment of the invention, the introducer 50 may be formed ofNitinol. Nitinol is preferred due to its flexibility, durability, andbiocompatibility. The introducer 50 may be constructed from a Nitinolwire that is ground to include a tapered small diameter tip. In analternative embodiment, the introducer 50 may be formed of multiplematerials or the same materials having different stiffnesses. As aresult, the introducer 50 may have sections that are more flexible thanadjacent sections of the same introducer 50. As a result, for example,the introducer 50 may have a first, stiff portion for guiding theintroducer 50 within the ductal lumen and a second, flexible portionthat allows the introducer 50 to conform to the shape of the ductallumen or lumen branch into which it is introduced. In any of theabove-discussed embodiments, the introducer 50 may be coated with aliquid or dry lubricant material that reduces the friction between theintroducer 50 and the breast duct during the introduction andadvancement of the introducer 50 in the duct.

The introducer 50 may be made of metal or plastics, including shapememory metals and plastics, and may have a tapered and/or an atraumatictip for gently probing and accessing a breast duct. Preferably, atapered tip 52 will extend distally of the catheter 40 during theintroduction of the catheter 40 into the breast duct. After access ofthe duct is complete, the catheter 40 may be slipped over the introducer50 and positioned at a location distal to the ductal sphincter.

In another embodiment of the invention, the proximal end of theintroducer 50 is formed into a ring shaped handle 51 (see FIGS. 14, 15and 17). The advantage of the ring shaped handle 51 is that is allowsthe device 10 to be used with one hand. The ring shaped handle 51 mayallow the practitioner to grasp the flexible side arms 100 of the device10 using their thumb and forefinger and to manipulate the introducer 50by using their index finger which may be positioned through the ringshaped handle 51. The ring shaped handle 51 may be constructed of athermoplastic such as ABS or polycarbonate or pellathane, and may beshaped in alternative forms that will allow the practitioner to operatethe device 10 with one hand.

During the process of introducing the catheter 40 into the duct, aductal opening is located on the surface of a nipple by a practitioneror attendant and an introducer 50 is advanced through the ductal openinginto the duct. The introducer 50 may be a long flexible guide wire, ashorter dilator or any of the other above-mentioned introducers. Priorto, or after the introducer 50 is positioned within the duct, themanifold hub 20 and catheter 40 may receive the introducer 50. Aspreviously discussed, compressing the flexible side arms 100 thusactuating the interlocking side arms 110 away from the fitting 70 mayopen the fitting 70. Once pressure is released from the flexible sidearms 100, the interlocking arms 110 are forced away from the manifoldhub 20 by the springs 120 thus closing the aperture 74 about thereceived introducer 50 to form a fluid tight seal at the distal end ofthe manifold hub 20 so that fluid does not exit the manifold hub 20around the introducer 50 during the insertion catheter 40 into the duct(See FIGS. 9, 10, 12, 13, 14, 15, and 16).

When the catheter 40 is positioned within the duct as intended, thefitting 70 is opened and the introducer 50 removed. The 70 may then beclosed again to seal the hub 20. Fluid is then introduced into themanifold hub 20, through the catheter 40 and into the breast duct untilresistance is met during the infusion. At this time, it is assumed thatthe duct is filled. The infusion tube, for example tube 34, may then beclosed and the fluid allowed to remain in the duct for a preselectedtime. During this preselected time, the breast may be massaged andsqueezed to stimulate mixing of the wash fluid and ductal fluid, andalso ultimately to encourage the fluid to leave the duct and enter themanifold hub 20. The collection tube, for example tube 36, may be openedand the breast squeezed to urge the fluid to progress through thecatheter 40 and into the manifold hub 20. If desired, when cloudy returnfluid is seen in the hub 20 (which may be transparent or include atransparent window), the infusion tube 34 may be opened and fluidinfused into the manifold hub 20 to push the ductal fluid sample thathas collected in the hub 20 into the collection tube 36 and a waitingcollection receptacle. Alternatively, and possibly additionally,aspiration pressure may be applied within the manifold hub 20 and at thecollection tube 36 to aspirate any fluid remaining in the hub 20 intothe collection receptacle. The process is repeated either followinganother infusion of fluid into the duct or by another round of squeezingto encourage return and collection of the infused fluid and cellularmaterial from within the breast duct.

In an embodiment, the method of lavage may include seating a patientsubstantially upright in a chair during the lavage procedure, ratherthan the standard or classic supine (face up) position. Alternatively,the patient may be ravaged in a prone position, face down, with nipplesand breast down. The prone face down position takes advantage of gravityand allows the breast ducts to drain into the collection receptacleduring the procedure when the outflow port is open. Thus, as discussedabove, the lavaging procedure may include infusing the breast duct witha wash fluid through an open inflow lumen while an outflow lumen isclosed; closing the inflow lumen when the duct is filled; squeezing ormassaging the breast or both; and opening the outflow lumen to collectthe wash fluid.

The cells collected may comprise ductal epithelial cells; the ductalfluid collected may comprise molecular and cellular material. Analysisof the ductal epithelial cells and/or the molecular and cellularmaterial in the ductal fluid may proceed as described below discussingthe diagnostic methods possible of these collected materials. Thecollected cells and fluid and fluid components may be analyzed. Thelavage fluid including the ductal cells may be analyzed for diagnosticpurposes. Conditions in a breast milk duct that are desirable todiagnose include a cancer or precancer condition. The precancercondition may include atypical ductal hyperplasia (ADH) or low-gradeductal carcinoma in situ (LG-DCIS). The diagnostic agent may also havethe ability to diagnose other breast related conditions, including, e.g.fibrotic, cystic or conditions relating to lactation. Diagnostic agentsmay be mixed with the ductal fluid (either in the lavage procedure, orafter the fluid is collected).

The fluid infused into the duct to lavage the duct may include known,biocompatible fluids. These lavage fluids may include saline, phosphatebuffered saline, a nonabsorbable fluid, an isotonic solution, an osmoticsolution, a hypotonic solution, and a hypertonic solution. The washfluid may comprise for example, saline, phosphate buffered saline, anonabsorbable fluid, an isotonic solution, an osmotic solution, ahypotonic solution, a hypertonic solution a protein, a colloid, a sugar,a polymer, mannitol, sorbitol, glucose, glycerol, sucrose, raffinose,fructose, lactulose, sodium chloride, polyethyleneglycol (PEG),maltodextrin, dextran (e.g. dextran 70), hydroxyethyl starch, fluidgelatin, a synthetic colloid, an antibody, a binding protein, oralbumin.

As mentioned above, a diagnostic or therapeutic agent may be introducedinto a breast duct through the manifold hub 20 and catheter 40. Theintroduced agent for infusing into the duct may comprise anon-absorbable fluid and/or an oncotic agent and/or an osmotic agent.The agent may be soluble. The agent may comprise a molecule that is aprotein, a colloid, a sugar, or a polymer. The agent may be mannitol,sorbitol, glucose, glycerol, sucrose, raffinose, fructose, lactulose,sodium chloride, polyethyleneglycol (PEG), maltodextrin, dextran (e.g.dextran 70), hydroxyethyl starch, fluid gelatin, or a synthetic colloid.The agent may comprise a protein and the protein may be a bindingprotein or an antibody. The binding protein may be albumin.Administering may comprise administering locally, and localadministration may comprise administering intraductally. A system forincreasing or standardizing an amount of fluid collectable from a milkduct of a breast may comprise infusing a nonabsorbable fluid and/or anosmotic agent and/or an oncotic agent into the ductal lumen, a medicaltool for delivering the agent to the ductal lumen, and instructions foruse.

Any number of alternative combinations could exist for defining theinvention, which incorporate one or more elements from thespecification, including the description, claims, and drawings, invarious combinations or sub combinations. It will be apparent to thoseskilled in the relevant technology, in light of the presentspecification, that alternate combinations of aspects of the invention,either alone or in combination with one or more elements or stepsdefined herein, may be utilized as modifications or alterations of theinvention or as part of the invention. It may be intended that thewritten description of the invention contained herein covers all suchmodifications and alterations.

1. A device for being introduced and positioned within a breast duct forintroducing or removing material within the breast duct, said apparatuscomprising: a manifold hub comprising a fitting for sealing about aductal introducer extending through said manifold hub at one end of saidmanifold hub said fitting including an aperture that may be repeatedlyopened and closed, the sides of said manifold hub comprising twoopposing flexible arms connected at one end to the base of said hub andunconnected at the other end and substantially parallel to one another,said arms are held in a sprung position such that said unconnected endsof said arms compress said fitting such that said aperture is closed andwhen said arms are compressed, said unconnected ends of said arms nolonger compress said fitting and said aperture is opened.
 2. The deviceof claim 1 wherein said sealing fitting is a silicone gasket.
 3. Thedevice of claim 1 wherein springs are located between said flexible armsand the body of said hub such that the springs keep said arms inactuated position.
 4. The device of claim 1 wherein the free ends ofsaid arms are interlocking hooks.
 5. The device of claim 1 wherein saidductal introducer has a ring shaped handle.
 6. The device of claim 1wherein said ductal introducer is made of Nitinol and has a distal tipthat tapers.
 7. The device of claim 1 wherein said introducer tapersfrom approximately 0.025 inches to approximately 0.008 inches.
 8. Amethod for obtaining cellular material from a human breast milk ductusing a device comprising a manifold hub comprising a fitting forsealing about a ductal introducer extending through said manifold hub atone end of said manifold hub said fitting including an aperture that maybe repeatedly opened and closed, the sides of said manifold hubcomprising two opposing flexible arms connected at one end to the baseof said hub and unconnected at the other end and substantially parallelto one another, said arms are held in a sprung position such that saidunconnected ends of said arms compress said fitting such that saidaperture is closed and when said arms are compressed, said unconnectedends of said arms no longer compress said fitting and said aperture isopened; and including the steps of: inserting the introducer into theinternal passageway of a breast duct; and advancing the catheter intothe breast duct.
 9. A method for obtaining cellular material from ahuman breast milk duct using a device comprising a manifold hubcomprising a fitting for sealing about a ductal introducer extendingthrough said manifold hub at one end of said manifold hub said fittingincluding an aperture that may be repeatedly opened and closed, thesides of said manifold hub comprising two opposing flexible armsconnected at one end to the base of said hub and unconnected at theother end and substantially parallel to one another, said arms are heldin a sprung position such that said unconnected ends of said armscompress said fitting such that said aperture is closed and when saidarms are compressed, said unconnected ends of said arms no longercompress said fitting and said aperture is opened; and including thesteps of: inserting the introducer into the internal passageway of abreast duct; advancing the sheath into the breast duct; and advancingthe catheter into the breast duct.